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    Pdk1 pyruvate dehydrogenase kinase, isoenzyme 1 [ Mus musculus (house mouse) ]

    Gene ID: 228026, updated on 27-Dec-2024

    Summary

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    Official Symbol
    Pdk1provided by MGI
    Official Full Name
    pyruvate dehydrogenase kinase, isoenzyme 1provided by MGI
    Primary source
    MGI:MGI:1926119
    See related
    Ensembl:ENSMUSG00000006494 AllianceGenome:MGI:1926119
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    B830012B01; D530020C15Rik
    Summary
    Predicted to enable ATP binding activity; identical protein binding activity; and pyruvate dehydrogenase (acetyl-transferring) kinase activity. Involved in regulation of acetyl-CoA biosynthetic process from pyruvate. Located in mitochondrion. Part of pyruvate dehydrogenase complex. Is expressed in several structures, including alimentary system; brain; genitourinary system; limb mesenchyme; and sensory organ. Orthologous to human PDK1 (pyruvate dehydrogenase kinase 1). [provided by Alliance of Genome Resources, Dec 2024]
    Annotation information
    Note: Pdk1 (Gene ID: 228026) and Pdpk1 (Gene ID: 18607) share the Pdk1 symbol/alias in common. Pdk1 is a widely used alternative name for 3-phosphoinositide dependent protein kinase 1 (Pdpk1), which can be confused with the official symbol for pyruvate dehydrogenase kinase, isoenzyme 1 (Pdk1). [03 Apr 2019]
    Expression
    Ubiquitous expression in heart adult (RPKM 12.2), thymus adult (RPKM 9.7) and 28 other tissues See more
    Orthologs
    human all
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    Genomic context

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    See Pdk1 in Genome Data Viewer
    Location:
    2 C3; 2 42.84 cM
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 2 NC_000068.8 (71703398..71734202)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 2 NC_000068.7 (71873215..71903858)

    Chromosome 2 - NC_000068.8Genomic Context describing neighboring genes Neighboring gene ribosomal protein S7 pseudogene Neighboring gene integrin alpha 6 Neighboring gene CapStarr-seq enhancer MGSCv37_chr2:71652164-71652396 Neighboring gene CapStarr-seq enhancer MGSCv37_chr2:71704749-71704932 Neighboring gene STARR-seq mESC enhancer starr_04811 Neighboring gene predicted gene, 46785 Neighboring gene predicted gene, 39845

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Pyruvate dehydrogenase kinase 1 participates in macrophage polarization via regulating glucose metabolism. Tan Z, et al. J Immunol, 2015 Jun 15. PMID 25964487, Free PMC Article
    2. Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation. Gerriets VA, et al. J Clin Invest, 2015 Jan. PMID 25437876, Free PMC Article
    3. Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes. Yao Y, et al. Cell Death Dis, 2023 Nov 7. PMID 37935660, Free PMC Article
    4. Regulatory role of PDK1 via integrated gene analysis of mitochondria-immune response in periodontitis. Sun X, et al. Gene, 2024 Aug 5. PMID 38657876
    5. Genetic inhibition of PDK1 robustly reduces plaque deposition and ameliorates gliosis in the 5×FAD mouse model of Alzheimer's disease. Ye X, et al. Neuropathol Appl Neurobiol, 2022 Dec. PMID 35881686

    See all (82) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Regulatory role of PDK1 via integrated gene analysis of mitochondria-immune response in periodontitis.
      Title: Regulatory role of PDK1 via integrated gene analysis of mitochondria-immune response in periodontitis.
    2. Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes.
      Title: Pyruvate dehydrogenase kinase 1 protects against neuronal injury and memory loss in mouse models of diabetes.
    3. PPP3CB Inhibits Cell Proliferation and the Warburg Effect in Bladder Cancer by Blocking PDHK1.
      Title: PPP3CB Inhibits Cell Proliferation and the Warburg Effect in Bladder Cancer by Blocking PDHK1.
    4. Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.
      Title: Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk.
    5. Deficiency of Pdk1 drives heart failure by impairing taurine homeostasis through Slc6a6.
      Title: Deficiency of Pdk1 drives heart failure by impairing taurine homeostasis through Slc6a6.
    6. Genetic inhibition of PDK1 robustly reduces plaque deposition and ameliorates gliosis in the 5xFAD mouse model of Alzheimer's disease.
      Title: Genetic inhibition of PDK1 robustly reduces plaque deposition and ameliorates gliosis in the 5×FAD mouse model of Alzheimer's disease.
    7. Pyruvate dehydrogenase kinase 1 and 2 deficiency reduces high-fat diet-induced hypertrophic obesity and inhibits the differentiation of preadipocytes into mature adipocytes.
      Title: Pyruvate dehydrogenase kinase 1 and 2 deficiency reduces high-fat diet-induced hypertrophic obesity and inhibits the differentiation of preadipocytes into mature adipocytes.
    8. Pyruvate dehydrogenase kinase is a negative regulator of interleukin-10 production in macrophages.
      Title: Pyruvate dehydrogenase kinase is a negative regulator of interleukin-10 production in macrophages.
    9. High PDK1 expression promotes breast cancer stemness.
      Title: Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia.
    10. HIF-1alpha-PDK1-mediated metabolic changes occur in mild hypoxia, where mitochondrial cytochrome c oxidase activity is unimpaired, suggesting a mode of glycolytic reprogramming.
      Title: HIF-1α-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity.
    Submit: New GeneRIF Correction See all GeneRIFs (16)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Endonuclease-mediated (4) 
    • Gene trapped (1) 
    • Targeted (5)  1 citation

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • D530020C15Rik

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables identical protein binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein serine/threonine kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables protein-containing complex binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables pyruvate dehydrogenase (acetyl-transferring) kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables pyruvate dehydrogenase (acetyl-transferring) kinase activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables pyruvate dehydrogenase (acetyl-transferring) kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in cell population proliferation ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in cell population proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cell surface receptor signaling pathway ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in hypoxia-inducible factor-1alpha signaling pathway ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in hypoxia-inducible factor-1alpha signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    acts_upstream_of_or_within intracellular signal transduction ISA
    Inferred from Sequence Alignment
    more info
    		  
    involved_in intrinsic apoptotic signaling pathway in response to oxidative stress ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in intrinsic apoptotic signaling pathway in response to oxidative stress ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in regulation of acetyl-CoA biosynthetic process from pyruvate IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of acetyl-CoA biosynthetic process from pyruvate IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of glucose metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of glucose metabolic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in regulation of glucose metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in mitochondrial matrix IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrion HDA PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane ISA
    Inferred from Sequence Alignment
    more info
    		  
    part_of pyruvate dehydrogenase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of pyruvate dehydrogenase complex ISO
    Inferred from Sequence Orthology
    more info
    		  

    General protein information

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    Preferred Names
    [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial; pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial
    Names
    PDH kinase 1
    [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial
    pyruvate dehydrogenase kinase, isozyme 1
    NP_001346931.1
    NP_766253.2
    XP_011237746.1
    XP_011237747.1
    XP_011237748.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001360002.1 → NP_001346931.1  [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform 2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) represents the use of an alternate promoter, resulting in a novel 5' UTR and the use of a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus compared to isoform 1.
      Source sequence(s)
      AL928963
      UniProtKB/TrEMBL
      Q8R2U8
      Conserved Domains (2) summary
      smart00387
      Location:192 → 312
      HATPase_c; Histidine kinase-like ATPases
      pfam10436
      Location:1 → 142
      BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

    2. NM_172665.5 → NP_766253.2  [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_766253.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AK046805, AK153649, AK165090, BE994546
      Consensus CDS
      CCDS16119.1
      UniProtKB/Swiss-Prot
      Q3U5E5, Q8BFP9
      UniProtKB/TrEMBL
      Q8R2U8
      Related
      ENSMUSP00000006669.6, ENSMUST00000006669.6
      Conserved Domains (3) summary
      smart00387
      Location:268 → 388
      HATPase_c; Histidine kinase-like ATPases
      COG0642
      Location:268 → 396
      BaeS; Signal transduction histidine kinase [Signal transduction mechanisms]
      pfam10436
      Location:56 → 218
      BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000068.8 Reference GRCm39 C57BL/6J

      Range
      71703398..71734202
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011239444.3 → XP_011237746.1  pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial isoform X1

      UniProtKB/TrEMBL
      Q8R2U8
      Conserved Domains (2) summary
      cd16929
      Location:259 → 425
      HATPase_PDK-like; Histidine kinase-like ATPase domain of pyruvate dehydrogenase kinase, branched-chain alpha-ketoacid dehydrogenase kinase and related domains
      pfam10436
      Location:56 → 255
      BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

    2. XM_011239445.4 → XP_011237747.1  pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial isoform X2

      See identical proteins and their annotated locations for XP_011237747.1

      UniProtKB/TrEMBL
      Q8R2U8
      Conserved Domains (2) summary
      cd16929
      Location:183 → 349
      HATPase_PDK-like; Histidine kinase-like ATPase domain of pyruvate dehydrogenase kinase, branched-chain alpha-ketoacid dehydrogenase kinase and related domains
      pfam10436
      Location:2 → 179
      BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

    3. XM_011239446.4 → XP_011237748.1  pyruvate dehydrogenase (acetyl-transferring) kinase isozyme 1, mitochondrial isoform X2

      See identical proteins and their annotated locations for XP_011237748.1

      UniProtKB/TrEMBL
      Q8R2U8
      Conserved Domains (2) summary
      cd16929
      Location:183 → 349
      HATPase_PDK-like; Histidine kinase-like ATPase domain of pyruvate dehydrogenase kinase, branched-chain alpha-ketoacid dehydrogenase kinase and related domains
      pfam10436
      Location:2 → 179
      BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

    RNA

    1. XR_003952294.2 RNA Sequence

    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8BFP9.2 GenPept UniProtKB/Swiss-Prot:Q8BFP9

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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